Work

Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment

Year: 2025

Type: article

Abstract: AIMS: Crisugabalin is a novel calcium channel α2δ subunit ligand and a highly selective oral gamma-aminobutyric acid (GABA) analogue developed for the treatment of diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). This study investigated pharmacokinetic properties and safety of crisugabalin in subjects with renal impairment. METHODS: This multicenter, nonrandomized, open-label Phase I study investigated the pharmacokinetics and safety of a single oral 20-mg dose of crisugabalin capsule in Chinese subjects with various degrees of renal function, categorized according to the absolute glomerular filtration rate (GFR). A total of 32 subjects (eight subjects per renal function category [normal, mild, moderate, or severe impairment]) were enrolled and completed the study. Blood samples were collected up to 72 h post-dose, along with fractionated urine samples. Active moiety exposures were calculated as the sum of unbound exposures for crisugabalin and its active metabolites. RESULTS: of plasma crisugabalin in patients with mild, moderate and severe renal impairment increased by 14.63%, 119.57% and 272.61%, respectively, compared to subjects with normal renal function. CONCLUSION: For patients with GFR < 60 mL/min, dosage adjustments of crisugabalin should be considered. To maintain comparable plasma drug concentrations in patients with impaired renal function, it is recommended that crisugabalin doses be decreased by approximately 50% for every 50% decline in GFR.

Source: British Journal of Clinical Pharmacology

DOI: 10.1002/bcp.70310